Reliability and Stability of Contingent Negative Variation

Reliability parameters of a test indicate the stability (and quality) of the test itself. Reliability coefficients greater than 0.70 suggest an attribute as being sufficiently stable over time to be characterized as a trait. Reliability parameters of contingent negative variation (CNV) amplitudes in 27 healthy individuals were determined using a test-retest design. CNV was recorded at Cz, with an interstimulus interval of 3 s, on 2 separate occasions: initial session and 10 days later. Correlation coefficients between the 2 recording sessions were 0.675 for the total-CNV (tCNV), 0.855 for the early component (iCNV), 0.631 for the late component (lCNV), and 0.420 for the post-imperative negative variation (PINV). Statistical retest parameters for Spearman Brown were 0.806 for tCNV, 0.922 for iCNV, 0.774 for lCNV, and 0.655 for PINV. The iCNV, more than the other parameters, remained stable over the period of 10 days. It is suggested that the described standardized CNV recording procedure ensures reproducible and stable results in healthy subjects.     

CNV-like potentials on the cortical surface associated with conditioning in head-restrained rats

Head-restrained rats were conditioned to perform a CNV task: to press a lever in response to an imperative auditory stimulus (S2) given 1.5 sec after a warning stimulus (S1) for a drop of jelly food. With an electrode on the surface of the forelimb cortex, (1) sharp wave complexes immediately after S1 and S2, and (2) a negative slow potential (SP) between S1 and S2, on which early and late components were discernible, were recorded in association with performance of this task. With the electrode at a depth of 2 mm in the same cortical area, the corresponding field potential showed a long-lasting positive shift in addition to the components of the surface potential. These monopolar recordings were obtained with respect to a common reference at the frontal sinus. The surface-minus-depth potential (the transcortical potential), consequently, showed a surface-negative tonic wave, confirming Pirch's report (1980). During extinction of this conditioning, the SP between S1 and S2 disappeared, while the sharp waves following S1 and S2 remained with little modification, suggesting that the sharp waves are a kind of evoked potential (EP) elicited by the stimuli.Recording from 5 surface electrodes set in an array over the left hemisphere contralateral to the used forelimb during development of the conditioning revealed not only a spatial distribution of the SP but also a transition of the potentials. As the conditioning progressed, the negativity of the early SP component tended to increase, while that of the late component tended to decrease and was confined to the sensorimotor cortex. The similarities of the rat cortical surface potentials to the human and monkey CNV in their wave form and function suggests that the rat brain can produce electrical activity analogous to the human CNV.     

Slow potentials of the prefrontal cortex in dogs and the classical secretory conditioned reflex

Slow potentials (CNV and component P300) were recorded in the medial part of the prefrontal cortex of dogs trained to classical secretory conditioned reflex and its differentiation. CNV increased when the conditioned stimulus was preceded by a signal of different meaning, as compared with CNV to the same conditioned signal following the stimulus of the same meaning; the greatest values of CNV and P300 were observed in response to differential stimulus preceded by a positive signal.     

Motor response information influence on CNV shape and resolution time

This study systematically investigates changes in CNV waveform shape and resolution time that result from the presentation of facilitatory, inhibitory, or no motor response (MR) information simultaneously with the warning (S1) or imperative (S2) stimulus of the S1-S2-MR CNV paradigm. Analyses indicate that the simultaneous presentation of S1 and information to produce or inhibit a MR attenuates initial CNV development. Further, when the S1 information is inhibitive, CNV development is retarded throughout. The contribution of an inhibitory psychological process during CNV development is proposed. The data also indicate that CNV resolution time is not dependent on the presence of a motor response. It is suggested that CNV resolution time is indicative of psychological completion or closure.     

Relation between warning stimuli and contingent negative variation in man

Seven right handed male students were submitted to standard and target paired auditory stimuli to determine the relationship between contingent negative variation (CNV) and the slow negative waves following non paired stimuli. The warning stimuli informed subjects whether or not the impending unconditional stimulus implied a motor response. Subjects were instructed to execute the motor task at less than one second after unconditional stimulus. They were informed that the standard warning stimulus would be followed by an additional stimulus which confirmed its detection. Recordings of standard warning stimulus condition showed a subsequent increase in CNV amplitude. This significant increase appeared to be related to an enhancement in the subject's expectation towards the additional stimulus. The lowered CNV voltage in target condition seemed to be linked to the instructions, which involved a motor preparation after the imperative stimuli occurrence. It is suggested that the CNV may represent not only a general anticipatory but also an orienting process related to the signal value of the warning stimulus.     

Working range of stimulus flux transduction determines dendrite size and relative number of pheromone component receptor neurons in moths

We are proposing that the "relative" abundances of the differently tuned pheromone-component-responsive olfactory receptor neurons (ORNs) on insect antennae are not a result of natural selection working to maximize absolute sensitivity to individual pheromone components. Rather, relative abundances are a result of specifically tuned sensillum-plus-ORN units having been selected to accurately transduce and report to the antennal lobe the maximal ranges of molecular flux imparted by each pheromone component in every plume strand. To not reach saturating stimulus flux levels from the most concentrated plume strands of a pheromone blend, the dendritic surface area of the ORN type that is tuned to the most abundant component of a pheromone blend is increased in dendritic diameter in order to express a greater number of major pheromone component-specific odorant receptors. The increased ability of these enlarged dendrite, major component-tuned ORNs to accurately report very high flux of its component results in a larger working range of stimulus flux able to be accurately transduced by that type of ORN. However, the larger dendrite size and possibly other high-flux adjustments in titers of pheromone-binding proteins and degrading enzymes cause a decrease in absolute sensitivity to lower flux levels of the major component in lower concentration strands of the pheromone blend. In order to restore the ability of the whole-antenna major pheromone component-specific channel to accurately report to its glomerulus the abundance of the major component in lower concentration strands, the number of major component ORNs over the entire antenna is adjusted upward, creating a greater proportion of major component-tuned ORNs than those tuned to minor components. Pheromone blend balance reported by the whole-antennal major and minor component channels in low plume-flux strands is now restored, and the relative fluxes of the 2 components occurring in both low- and high-flux strands are thereby accurately reported to the component-specific glomeruli. Thus, we suggest that the 2 phenomena, dendrite size and relative numbers of differentially tuned ORNs are linked, and both are related to wide disparities in molecular flux ranges occurring for the more abundant and less abundant components in the pheromone blend plume strands.     

Neurophysiological Determinants of Tic Severity in Children with Chronic Motor Tic Disorder

Tics wax and wane in severity. Although the understanding of the natural course of symptoms in tic disorder (TD) is important for planning and assessing therapeutic interventions, neurophysiological mechanisms and predictors of tic exacerbation and remission have not been sufficiently investigated. In each of seven children suffering from TD, contingent negative variation (CNV) was recorded on 10 occasions over a period of 2 months. CNV parameters of children with TD were compared with CNV data of healthy, age-matched children. During the entire time of observation, tic severity was assessed by parents and the investigator using a scale developed from the Yale Global Tic Severity Scale. Moreover, tic severity was also evaluated using video assessments. Patients with TD were characterized by significantly lower amplitude of the total CNV and more pronounced habituation of the early CNV component as compared to healthy children. Correlation analysis between tic severity and CNV parameters demonstrated that the more severe the tics were, the lower the amplitude of the total CNV. Since CNV amplitude represents processes of resource mobilization and control over neuronal excitability, tic severity may result from less ability to control neurophysiological functions in patients with TD.     

Temporo-Spatial Dynamics of Event-Related EEG Beta Activity during the Initial Contingent Negative Variation

In the electroencephalogram (EEG), early anticipatory processes are accompanied by a slow negative potential, the initial contingent negative variation (iCNV), occurring between 500 and 1500 ms after cue onset over prefrontal cortical regions in tasks with cue-target intervals of about 3 s or longer. However, the temporal sequence of the distributed cortical activity contributing to iCNV generation remains unclear. During iCNV generation, selectively enhanced low-beta activity has been reported. Here we studied the temporal order of activation foci in cortical regions assumed to underlie iCNV generation using source reconstruction of low-beta (13–18 Hz) activity. During the iCNV, elicited by a cued simple reaction-time task, low-beta power peaked first (750 ms after cue onset) in anterior frontal and limbic regions and last (140 ms later) in posterior areas. This activity occurred 3300 ms before target onset and provides evidence for the temporally ordered involvement of both cognitive-control and motor-preparation processes already at early stages during the preparation for speeded action.     

Locus of Psychological Control and Peculiarities of Event-Related EEG Potentials

In a group including 74 adults of both sexes, we examined interrelations between the locus of psychological control (diagnosed using the Rotter questionnaire) and parameters of event-related EEG potentials, ERPs, recorded in the course of performance of two behavioral test acts with a motor component. Task A corresponded to maximally fast pushing on the button after a signal with warning; the time of the sensorimotor reaction was measured. Task B included internal counting of a definite time interval limited by two pushings on the button. Under these conditions, we recorded the contingent negative variation (CNV), the P300 potential, and, in task B, the readiness potential (RP). EEG leads C3 and C4, according to the 10-20 system, were used. Internals (estimates by the questionnaire, 6 stens or higher) were characterized by higher amplitudes of the terminal CNV (CNV-T), integral CNV, and P300 in task A, by greater RP and CNV amplitudes in task B, and also by shorter reaction times and their smaller dispersion. It should be supposed that the corresponding peculiarities of the neurodynamic constitution of an individual are determined, to a considerable extent, by the specificity of organization and functioning of a few neurotransmitter (aminergic in particular) and neurohumoral systems.     

Ontogenetic characteristics of the development of slow negative and positive potentials during the performance of a visual perceptive task

In age aspect, topography and parameters were studied of late EPs and slow negative components (CNV) to successively presented visual stimuli: the preliminary signal and two compared contour images. Age characteristics of development of the frontal negativity N450 and the late positive complex (LPC) were revealed. in children 7 and 10 years old, the component N450 was present in response both to the preliminary and the first stimulus in the compared pair; LPC was recorded to all three presented visual stimuli. In 17 years old subjects and in adults, selectivity of N450 formation in the EP to the first of the compared stimuli and LPC to the second (imperative) stimulus correlates with involvement of rostral brain areas--central in youths, central and frontal ones in adults--both in the process of waiting (CNV) and evaluation of coming information (LPC).     

A duplication CNV that conveys traits reciprocal to metabolic syndrome and protects against diet-induced obesity in mice and men

The functional contribution of CNV to human biology and disease pathophysiology has undergone limited exploration. Recent observations in humans indicate a tentative link between CNV and weight regulation. Smith-Magenis syndrome (SMS), manifesting obesity and hypercholesterolemia, results from a deletion CNV at 17p11.2, but is sometimes due to haploinsufficiency of a single gene, RAI1. The reciprocal duplication in 17p11.2 causes Potocki-Lupski syndrome (PTLS). We previously constructed mouse strains with a deletion, Df(11)17, or duplication, Dp(11)17, of the mouse genomic interval syntenic to the SMS/PTLS region. We demonstrate that Dp(11)17 is obesity-opposing; it conveys a highly penetrant, strain-independent phenotype of reduced weight, leaner body composition, lower TC/LDL, and increased insulin sensitivity that is not due to alteration in food intake or activity level. When fed with a high-fat diet, Dp(11)17/+ mice display much less weight gain and metabolic change than WT mice, demonstrating that the Dp(11)17 CNV protects against metabolic syndrome. Reciprocally, Df(11)17/+ mice with the deletion CNV have increased weight, higher fat content, decreased HDL, and reduced insulin sensitivity, manifesting a bona fide metabolic syndrome. These observations in the deficiency animal model are supported by human data from 76 SMS subjects. Further, studies on knockout/transgenic mice showed that the metabolic consequences of Dp(11)17 and Df(11)17 CNVs are not only due to dosage alterations of Rai1, the predominant dosage-sensitive gene for SMS and likely also PTLS. Our experiments in chromosome-engineered mouse CNV models for human genomic disorders demonstrate that a CNV can be causative for weight/metabolic phenotypes. Furthermore, we explored the biology underlying the contribution of CNV to the physiology of weight control and energy metabolism. The high penetrance, strain independence, and resistance to dietary influences associated with the CNVs in this study are features distinct from most SNP-associated metabolic traits and further highlight the potential importance of CNV in the etiology of both obesity and MetS as well as in the protection from these traits.     

Effects of neck flexion on contingent negative variation and anticipatory postural control during arm movement while standing

We investigated the effects of neck flexion on contingent negative variation (CNV) and anticipatory postural control using an arm flexion task in standing. CNV was adopted to evaluate the state of activation of brain areas related to anticipatory postural control. Subjects were required to flex the arms in response to a sound stimulus preceded by a warning sound stimulus. Two different intervals (2.0 and 3.5 s) between these two stimuli were used in neck position in quiet standing (neck resting) and neck position at 80% angle of maximal neck flexion. The mean amplitude of CNV 100-ms before the response stimulus, recorded from a Cz electrode, was calculated. Onset timing of activation of the postural muscles (lumbar paraspinal, biceps femoris and gastrocnemius) with respect to the anterior deltoid was analyzed. Reaction time at the anterior deltoid was significantly shorter in the 2.0 s period than in the 3.5 s period, and in the neck flexion than in the neck resting in both periods. In the 2.0 s, but not in the 3.5 s period, neck flexion resulted in an increased CNV amplitude and an increased duration of preceding activation of the postural muscles, and the correlation between these increases was significant.     

Long latency auditory evoked potentials: intensity, inter-stimulus interval, and habituation

Experiment 1 elicited the P1, N1, P2, and N2 components of the long latency auditory evoked potential (AEP) using a 1000 Hz tone presented at 30, 50, or 70 dB SPL and 1-, 3-, or 5-second inter-stimulus intervals to assess the relative effects of the combination of these variables on component amplitude and latency. Four blocks of 16 tone presentations each were recorded from each subject to determine if changes in the AEP would occur because of short-term habituation. Both stimulus factors interacted significantly in a systematic fashion for the amplitude measures, with increases in latency also associated with increases in intensity and inter-stimulus interval. Only minor changes across the four trial blocks for either the amplitude or latency measures were observed over the various stimulus presentation conditions. Experiment 2 employed the same tone stimulus presented at 50 dB SPL and a 3-second inter-stimulus interval. Eight blocks of 64 trials were recorded from each subject on each day for four days to investigate long-term habituation effects. No substantial changes in any of the component amplitudes or latencies were obtained across the 32 trial blocks. It was concluded that intensity and inter-stimulus interval interact to determine AEP amplitude as well as latency values and that the constituent components do not change appreciably with repeated stimulus presentations, even after several days.     

Adaptation changes in dynamic postural control and contingent negative variation during backward disturbance by transient floor translation in the elderly

ABSTRACT: BACKGROUND: We investigated adaptation changes in dynamic postural control and contingent negative variation (CNV) in 13 young and 12 elderly adults. Subjects repeatedly underwent backward postural disturbance by a forward floor translation (S2) 2 s after an auditory warning signal (S1). Initial and second sets were conducted, each set with 20 trials. Posterior peak position of the center of pressure in the anteroposterior direction (CoPy) after S2 was identified. Electroencephalograms from Cz were averaged for each set, and the CNV negative peak was identified. RESULTS: Compared with the first trial, the posterior peak position of CoPy changed significantly forward from the 12th trial in the young and from the 19th trial in the elderly during the initial set. The mean of the posterior peak position was more forward in second set than in the initial set for both groups and was significantly backward in the elderly compared to the young for both sets. These findings indicate that subjects in both groups adapted better to the postural disturbance in the second set than in the initial set, and the adaptation was later in the elderly. Late CNV in the young started to increase negatively from the middle of the S1-S2 period and peaked just before S2. Peak CNV amplitude was larger in the second set than in the initial set. In contrast, late CNV in the elderly exhibited no negative increase as in the young and peaked in the middle of the S1-S2 period, which was followed by gradual decreasing toward S2. No adaptive changes were found in late CNV for the elderly. CONCLUSIONS: It is conceivable that reduced activation of the frontal lobe may be one of the factors contributing to the decrease in postural adaptability in the elderly. The elderly may use various brain regions for the adaptation of dynamic postural control compared with the young.     

Analysis of copy number variants in the cattle genome

Copy number variation (CNV) is likely to be an important component of heritable variation in livestock. To characterise CNVs in cattle, we performed a genome wide survey to determine the number, location and gene content of these genomic features. A tiling oligonucleotide array with ~385,000 probes was used for comparative genomic hybridisation of both taurine and zebu cattle. Using a conservative set of calling criteria, a total of 51 CNV were detected that collectively spanned approximately half of one percent of the bovine genome. The size of the average CNV within each animal ranged from 213 kb up to 335 kb. Half of the CNV were detected in a single animal only, whilst the remainder was independently identified in multiple individuals. Analysis was performed to determine the gene content for each CNV region. This revealed that the majority of CNV (82%) spanned at least one gene, with a number of CNV containing genes which are known to control aspects of phenotypic variation in cattle. Whilst additional studies are required to determine the impact of individual CNV, this study confirmed them as an important class of genomic variation in cattle.     

Spatial cueing,sensory gating and selective response preparation: an ERP study on visuo-spatial orienting

Event-related brain potentials (ERPs) were recorded in a visuo-spatial attention task where the position of an imperative stimulus was indicated either validly or invalidly by a central arrow (trial-by-trial cueing). Subjects had to perform choice RT tasks with the response being dependent either on the identity of the target stimulus or on its position. When target identity was relevant for response selection, validly cued stimuli elicited amplitude enhancements of the early, sensory-evoked P1 and N1 components at lateral posterior sites. The N1 validity effect was limited to scalp sites ipsilateral to the visual field of stimulus presentation. Although these effects were found only when the sensory discrimination task was considerably difficult, they are in line with models assuming that modulations of sensory-perceptual processing (“sensory gating”) are induced by spatial cueing. However, when target location was response-relevant, N1 amplitude enhancements were consistently elicited by invalidly cued letters.CNV and LRP measures indicated that the arrow elicited response-related processing in the cue-target interval. Such processes occurred even when the cue contained no information about an upcoming response. Two consecutive lateralization phases were distinguishable in the LRP, with experimentally induced response assignments becoming effective only during the second phase.     

An efficient method for measuring copy number variation applied to improvement of nematode resistance in soybean

Copy number variation (CNV) is implicated in important traits in multiple crop plants, but can be challenging to genotype using conventional methods. The Rhg1 locus of soybean, which confers resistance to soybean cyst nematode (SCN), is a CNV of multiple 31.2‐kb genomic units each containing four genes. Reliable, high‐throughput methods to quantify Rhg1 and other CNVs for selective breeding were developed. The CNV genotyping assay described here uses a homeologous gene copy within the paleopolyploid soybean genome to provide the internal control for a single‐tube TaqMan copy number assay. Using this assay, CNV in breeding populations can be tracked with high precision. We also show that extensive CNV exists within Fayette, a released, inbred SCN‐resistant soybean cultivar with a high copy number at Rhg1 derived from a single donor parent. Copy number at Rhg1 is therefore unstable within a released variety over a relatively small number of generations. Using this assay to select for individuals with altered copy number, plants were obtained with both increased copy number and increased SCN resistance relative to control plants. Thus, CNV genotyping technologies can be used as a new type of marker‐assisted selection to select for desirable traits in breeding populations, and to control for undesirable variation within cultivars.     

Phasic influences of vagal stimulation on atrioventricular conduction

The beat-by-beat changes in atrioventricular (AV) conduction evoked by constant frequency and phase-coupled vagal stimulation were examined both qualitatively and quantitatively in 13 anesthetized dogs. The effects of pacing cycle length and sympathetic activity on the vagally induced phasic changes in AV conduction were also characterized. When the vagal stimulus interval was nearly equal to the pacing cycle length and the vagal stimulus moved progressively through the cardiac cycle, AV interval oscillated in a rhythmic fashion. The rhythmicity of the vagally induced AV interval oscillations was altered substantially by changes in either the vagal stimulus interval or the pacing cycle length. The vagally induced AV interval oscillations were abolished during phase-coupled vagal stimulation; however, the magnitude of the resultant steady-state AV interval depended on the time relative to the phase of the cardiac cycle that the vagal stimulus was delivered. In the presence or absence of sympathetic stimulation, a vagal stimulus falling approximately 200 ms prior to atrial depolarization evoked the greatest prolongation in AV interval, regardless of the pacing cycle length. Additionally, the effects of combined sympathetic and phase-dependent vagal stimulation on the AV interval were additive. These data confirm that the influence of a vagal stimulus on AV interval can be predicted from the phase in the cardiac cycle that the vagal stimulus is delivered. Moreover, this phase dependency of vagal effects evokes marked qualitative variations in AV interval response patterns when either the vagal stimulus interval or the pacing cycle length is altered.     

Psychological distance to reward in monkeys

A concurrent-chains schedule was employed to examine crab-eating macaques' choice between segmented and unsegmented fixed-interval 30-s schedules. A stimulus change occurred during one of the fixed-interval schedules (segmented schedule), while no stimulus change occurred during the other (unsegmented schedule). The subjects were exposed to three consecutive stimulus-change conditions, in an attempt to explore whether correlation of the stimulus changes with a fixed interval of nonreinforcement affects the preference between the alternatives. When the stimulus change always occurred at a half point of the segmented schedule (the first and third conditions), all subjects preferred the fixed-interval schedule without stimulus changes. This replicated previous findings with pigeons and humans. On the other hand, when the intervals before and after the stimulus change varied on every entry to the segmented schedule with the sum of them being constant (the second condition), the subjects were indifferent to the alternatives. These results are consistent with the view that the preference for unsegmented schedules over segmented ones might be due to aversiveness which the initial component in the segmented schedule possesses as a result of its correlation with a fixed interval of nonreinforcement.     

CCR3 and choroidal neovascularization

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV.